Significance of Size, Surface Chemistry and Morphology in Nanodrugs Behavior: A Mini-review
الموضوعات : Biotechnological Journal of Environmental Microbiology
1 - Department of Microbiology, Faculty of Basic Sciences, Lahijan Branch, Lahijan, Iran
الکلمات المفتاحية: Nanoparticle, Nanodrug, Physio-chemical properties,
ملخص المقالة :
Nanoparticles (NPs) have increasingly captured attention as high potential anticancer drugs over the years. A categorization of this landscape can immensely propel organized comparative research in the future and bring deeper understanding of nanomaterials’ comportment in biological settings. Although diverse, all nano platforms pursue similar goals of increasing efficacy in the four domains of oncology known as; diagnosis, treatment, drug delivery, and detection of biomarkers. In this review, we have gathered and provided a class-affiliated rendering of the most recent wet-lab research exploring the impacts of size, surface chemistry, and morphology in various aspects of cancer care. Efforts here are focused on defining parameters for physicochemical properties of NPs and demonstrating variable attributes of them with regard to each. The said goal is achieved by i) grouping NPs under parameters of size, surface properties, and shape, ii) listing major types of NP within each group, and iii) arranging diverse and well-trusted original research done on cancer control over the past years.
المصادر:
Agudo-Canalejo, J., & Lipowsky, R. (2016). Stabilization of membrane necks by adhesive particles, substrate surfaces, and constriction forces. Soft Matter, 12(39), 8155–8166. https://doi.org/10.1039/C6SM01481J
AlSawaftah, N. M., Awad, N. S., Pitt, W. G., & Husseini, G. A. (2022). pH-Responsive Nanocarriers in Cancer Therapy. Polymers, 14(5), 936. https://doi.org/10.3390/polym14050936
Avila, Y. I., Rebolledo, L. P., Leal Santos, N., Rawlins, B., Radwan, Y., Andrade-Muñoz, M., Skelly, E., Chandler, M. R., Andrade, L. N. S., Kim, T. J., Dobrovolskaia, M. A., & Afonin, K. A. (2025). Changes in Generations of PAMAM Dendrimers and Compositions of Nucleic Acid Nanoparticles Govern Delivery and Immune Recognition. ACS Biomaterials Science & Engineering, 11(6), 3726–3737. https://doi.org/10.1021/acsbiomaterials.5c00336
Banerjee, A., Qi, J., Gogoi, R., Wong, J., & Mitragotri, S. (2016). Role of nanoparticle size, shape and surface chemistry in oral drug delivery. Journal of Controlled Release, 238, 176–185. https://doi.org/10.1016/j.jconrel.2016.07.051
Barz, M., Parak, W. J., & Zentel, R. (2024). Concepts and Approaches to Reduce or Avoid Protein Corona Formation on Nanoparticles: Challenges and Opportunities. Advanced Science (Weinheim, Baden-Wurttemberg, Germany), 11(34), e2402935. https://doi.org/10.1002/advs.202402935
Behzadi, S., Serpooshan, V., Tao, W., Hamaly, M. A., Alkawareek, M. Y., Dreaden, E. C., Brown, D., Alkilany, A. M., Farokhzad, O. C., & Mahmoudi, M. (2017). Cellular uptake of nanoparticles: journey inside the cell. Chemical Society Reviews, 46(14), 4218–4244. https://doi.org/10.1039/c6cs00636a
Bertrand, N., Grenier, P., Mahmoudi, M., Lima, E. M., Appel, E. A., Dormont, F., Lim, J.-M., Karnik, R., Langer, R., & Farokhzad, O. C. (2017). Mechanistic understanding of in vivo protein corona formation on polymeric nanoparticles and impact on pharmacokinetics. Nature Communications, 8(1), 777. https://doi.org/10.1038/s41467-017-00600-w
Bhirde, A. A., Chikkaveeraiah, B. V., Srivatsan, A., Niu, G., Jin, A. J., Kapoor, A., Wang, Z., Patel, S., Patel, V., Gorbach, A. M., Leapman, R. D., Gutkind, J. S., Hight Walker, A. R., & Chen, X. (2014). Targeted Therapeutic Nanotubes Influence the Viscoelasticity of Cancer Cells to Overcome Drug Resistance. ACS Nano, 8(5), 4177–4189. https://doi.org/10.1021/nn501223q
Campu, A., Focsan, M., Lerouge, F., Borlan, R., Tie, L., Rugina, D., & Astilean, S. (2020). ICG-loaded gold nano-bipyramids with NIR activatable dual PTT-PDT therapeutic potential in melanoma cells. Colloids and Surfaces B: Biointerfaces, 194, 111213. https://doi.org/10.1016/j.colsurfb.2020.111213
Carnovale, C., Bryant, G., Shukla, R., & Bansal, V. (2019). Identifying Trends in Gold Nanoparticle Toxicity and Uptake: Size, Shape, Capping Ligand, and Biological Corona. ACS Omega, 4(1), 242–256. https://doi.org/10.1021/acsomega.8b03227
Cojocaru, E., Petriș, O. R., & Cojocaru, C. (2024). Nanoparticle-Based Drug Delivery Systems in Inhaled Therapy: Improving Respiratory Medicine. Pharmaceuticals, 17(8), 1059. https://doi.org/10.3390/ph17081059
Curthoys, N. P., & Moe, O. W. (2014). Proximal Tubule Function and Response to Acidosis. Clinical Journal of the American Society of Nephrology, 9(9), 1627–1638. https://doi.org/10.2215/CJN.10391012
Cybulski, P., Bravo, M., Chen, J. J.-K., Van Zundert, I., Krzyzowska, S., Taemaitree, F., Uji-i, H., Hofkens, J., Rocha, S., & Fortuni, B. (2025a). Nanoparticle accumulation and penetration in 3D tumor models: the effect of size, shape, and surface charge. Frontiers in Cell and Developmental Biology, 12. https://doi.org/10.3389/fcell.2024.1520078
Cybulski, P., Bravo, M., Chen, J. J.-K., Van Zundert, I., Krzyzowska, S., Taemaitree, F., Uji-i, H., Hofkens, J., Rocha, S., & Fortuni, B. (2025b). Nanoparticle accumulation and penetration in 3D tumor models: the effect of size, shape, and surface charge. Frontiers in Cell and Developmental Biology, 12. https://doi.org/10.3389/fcell.2024.1520078
Deivayanai, V. C., Thamarai, P., Karishma, S., Saravanan, A., Yaashikaa, P. R., Vickram, A. S., Hemavathy, R. V., Kumar, R. R., Rishikesavan, S., & Shruthi, S. (2025). Advances in nanoparticle-mediated cancer therapeutics: Current research and future perspectives. Cancer Pathogenesis and Therapy, 3(4), 293–308. https://doi.org/10.1016/j.cpt.2024.11.002
Dolai, J., Mandal, K., & Jana, N. R. (2021). Nanoparticle Size Effects in Biomedical Applications. ACS Applied Nano Materials, 4(7), 6471–6496. https://doi.org/10.1021/acsanm.1c00987
Eroglu, Z., Ozer, M. S., & Metin, O. (2023). Black Phosphorus Quantum Dots/Carbon Nitride-Reduced Graphene Oxide Ternary Heterojunction as a Multifunctional Metal-Free Photocatalyst for Photooxidation Reactions. ACS Sustainable Chemistry & Engineering, 11(19), 7560–7572. https://doi.org/10.1021/acssuschemeng.3c01055
Fan, Y., Zhang, W., Iqbal, Z., Li, X., Lin, Z., Wu, Z., Li, Q., Dong, H., Zhang, X., Gong, P., & Liu, P. (2024). Rod-shaped mesoporous silica nanoparticles reduce bufalin cardiotoxicity and inhibit colon cancer by blocking lipophagy. Lipids in Health and Disease, 23(1), 318. https://doi.org/10.1186/s12944-024-02301-y
Fang, W., Yu, K., Zhang, S., Jiang, L., Zheng, H., Huang, Q., & Li, F. (2024). Shape Matters: Impact of Mesoporous Silica Nanoparticle Morphology on Anti-Tumor Efficacy. Pharmaceutics, 16(5), 632. https://doi.org/10.3390/pharmaceutics16050632
Foroozandeh, P., & Aziz, A. A. (2018). Insight into Cellular Uptake and Intracellular Trafficking of Nanoparticles. Nanoscale Research Letters, 13(1), 339. https://doi.org/10.1186/s11671-018-2728-6
Gimondi, S., Vieira de Castro, J., Reis, R. L., Ferreira, H., & Neves, N. M. (2023). On the size-dependent internalization of sub-hundred polymeric nanoparticles. Colloids and Surfaces B: Biointerfaces, 225, 113245. https://doi.org/10.1016/j.colsurfb.2023.113245
Gospodinova, Z., Hristova-Panusheva, K., Kamenska, T., Antov, G., & Krasteva, N. (2025). Insights into cellular and molecular mechanisms of graphene oxide nanoparticles in photothermal therapy for hepatocellular carcinoma. Scientific Reports, 15(1), 15541. https://doi.org/10.1038/s41598-025-99317-w
Guo, Q., Pospischil, A., Bhuiyan, M., Jiang, H., Tian, H., Farmer, D., Deng, B., Li, C., Han, S.-J., Wang, H., Xia, Q., Ma, T.-P., Mueller, T., & Xia, F. (2016). Black Phosphorus Mid-Infrared Photodetectors with High Gain. Nano Letters, 16(7), 4648–4655. https://doi.org/10.1021/acs.nanolett.6b01977
Iqbal, S., Schneider, T.-J. K., Truong, T. T., Ulrich-Müller, R., Nguyen, P.-H., Ilyas, S., & Mathur, S. (2024). Carriers for hydrophobic drug molecules: lipid-coated hollow mesoporous silica particles, and the influence of shape and size on encapsulation efficiency. Nanoscale, 16(23), 11274–11289. https://doi.org/10.1039/D4NR01420K
Jiang, J., Hu, J., Li, M., Luo, M., Dong, B., Sitti, M., & Yan, X. (2025). NIR‐II Fluorescent Thermophoretic Nanomotors for Superficial Tumor Photothermal Therapy. Advanced Materials, 37(10). https://doi.org/10.1002/adma.202417440
Khajegi, P., & Rashidi-Huyeh, M. (2021). Optical Properties of Gold Nanoparticles: Shape and Size Effects. International Journal of Optics and Photonics, 15(1), 41–48. https://doi.org/10.52547/ijop.15.1.41
Kondorskiy, A. D., & Lebedev, V. S. (2021). Size and Shape Effects in Optical Spectra of Silver and Gold Nanoparticles. Journal of Russian Laser Research, 42(6), 697–712. https://doi.org/10.1007/s10946-021-10012-3
Korangath, P., Barnett, J. D., Sharma, A., Henderson, E. T., Stewart, J., Yu, S.-H., Kandala, S. K., Yang, C.-T., Caserto, J. S., Hedayati, M., Armstrong, T. D., Jaffee, E., Gruettner, C., Zhou, X. C., Fu, W., Hu, C., Sukumar, S., Simons, B. W., & Ivkov, R. (2020). Nanoparticle interactions with immune cells dominate tumor retention and induce T cell-mediated tumor suppression in models of breast cancer. Science Advances, 6(13), eaay1601. https://doi.org/10.1126/sciadv.aay1601
Kshirsagar, P. G., De Matteis, V., Pal, S., & Sangaru, S. S. (2023). Silver–Gold Alloy Nanoparticles (AgAu NPs): Photochemical Synthesis of Novel Biocompatible, Bimetallic Alloy Nanoparticles and Study of Their In Vitro Peroxidase Nanozyme Activity. Nanomaterials, 13(17), 2471. https://doi.org/10.3390/nano13172471
Lavín Flores, A., Medina-Berríos, N., Pantoja-Romero, W., Berríos Plaza, D., Kisslinger, K., Beltran-Huarac, J., Morell, G., & Weiner, B. R. (2024). Geometry and Surface Area Optimization in Iron Oxide Nanoparticles for Enhanced Magnetic Properties. ACS Omega. https://doi.org/10.1021/acsomega.4c03988
Li, Q., Liu, W., Liu, K., Dong, Z., Kong, W., Lu, X., Wei, Y., Wu, W., Yang, J., & Qi, J. (2024). The Role of Nanoparticle Morphology on Enhancing Delivery of Budesonide for Treatment of Inflammatory Bowel Disease. ACS Applied Materials & Interfaces, 16(26), 33081–33092. https://doi.org/10.1021/acsami.4c05214
Li, Y., Kröger, M., & Liu, W. K. (2015). Shape effect in cellular uptake of PEGylated nanoparticles: comparison between sphere, rod, cube and disk. Nanoscale, 7(40), 16631–16646. https://doi.org/10.1039/C5NR02970H
Liu, Y., Li, Y., Shen, W., Li, M., Wang, W., & Jin, X. (2024). Trend of albumin nanoparticles in oncology: a bibliometric analysis of research progress and prospects. Frontiers in Pharmacology, 15. https://doi.org/10.3389/fphar.2024.1409163
Lu, M., Liu, Y., Zhu, J., Shang, J., Bai, L., Jin, Z., Li, W., Hu, Y., Zheng, X., & Qian, J. (2025). Mapping the intellectual structure and emerging trends on nanomaterials in colorectal cancer: a bibliometric analysis from 2003 to 2024. Frontiers in Oncology, 14. https://doi.org/10.3389/fonc.2024.1514581
Lu, Y., Pan, X., Nie, Q., Zhou, Z., Dai, X., & Liu, O. (2023). Administration methods of lipid-based nanoparticle delivery systems for cancer treatment. Biomaterials Science, 11(11), 3800–3812. https://doi.org/10.1039/D3BM00219E
Lynn, A. Y., Shin, K., Eaton, D. A., Rose, M., Zhang, X., Ene, M., Grundler, J., Deschenes, E., Rivero, R., Bracaglia, L. G., Glazer, P. M., Stitelman, D. H., & Saltzman, W. M. (2025). Investigation of the protein corona and biodistribution profile of polymeric nanoparticles for intra-amniotic delivery. Biomaterials, 320, 123238. https://doi.org/10.1016/j.biomaterials.2025.123238
Ma, C., Zhang, J., Zhang, T., Sun, H., Wu, J., Shi, J., & Xie, Z. (2019). Comparing the Rod-Like and Spherical BODIPY Nanoparticles in Cellular Imaging. Frontiers in Chemistry, 7. https://doi.org/10.3389/fchem.2019.00765
Ma, X., Lee, S., Fei, X., Fang, G., Huynh, T., Chen, C., Chai, Z., Ge, C., & Zhou, R. (2020). Proteasome activity regulated by charged gold nanoclusters: Implications for neurodegenerative diseases. Nano Today, 35, 100933. https://doi.org/10.1016/j.nantod.2020.100933
Mai, B. T., Balakrishnan, P. B., Barthel, M. J., Piccardi, F., Niculaes, D., Marinaro, F., Fernandes, S., Curcio, A., Kakwere, H., Autret, G., Cingolani, R., Gazeau, F., & Pellegrino, T. (2019). Thermoresponsive Iron Oxide Nanocubes for an Effective Clinical Translation of Magnetic Hyperthermia and Heat-Mediated Chemotherapy. ACS Applied Materials & Interfaces, 11(6), 5727–5739. https://doi.org/10.1021/acsami.8b16226
Moscatiello, G. Y., Natale, C., Inserra, M., Morelli, A., Russo, L., Battajini, N., Sironi, L., Panzeri, D., Corbelli, A., De Luigi, A., Fiordaliso, F., Candiani, G., Bigini, P., & Diomede, L. (2025). The surface charge both influences the penetration and safety of polystyrene nanoparticles despite the protein corona formation. Environmental Science: Nano, 12(5), 2857–2870. https://doi.org/10.1039/D4EN00962B
Murugan, K., Choonara, Y. E., Kumar, P., Bijukumar, D., du Toit, L. C., & Pillay, V. (2015). Parameters and characteristics governing cellular internalization and trans-barrier trafficking of nanostructures. International Journal of Nanomedicine, 10, 2191–2206. https://doi.org/10.2147/IJN.S75615
Naumenko, V., Nikitin, A., Kapitanova, K., Melnikov, P., Vodopyanov, S., Garanina, A., Valikhov, M., Ilyasov, A., Vishnevskiy, D., Markov, A., Golyshev, S., Zhukov, D., Alieva, I., Abakumov, M., Chekhonin, V., & Majouga, A. (2019). Intravital microscopy reveals a novel mechanism of nanoparticles excretion in kidney. Journal of Controlled Release, 307, 368–378. https://doi.org/10.1016/j.jconrel.2019.06.026
Pang, C., Brunelli, A., Zhu, C., Hristozov, D., Liu, Y., Semenzin, E., Wang, W., Tao, W., Liang, J., Marcomini, A., Chen, C., & Zhao, B. (2015). Demonstrating approaches to chemically modify the surface of Ag nanoparticles in order to influence their cytotoxicity and biodistribution after single dose acute intravenous administration. Nanotoxicology, 1–11. https://doi.org/10.3109/17435390.2015.1024295
Peng, Y., Yang, Z., Sun, H., Li, J., Lan, X., & Liu, S. (2024). Nanomaterials in Medicine: Understanding Cellular Uptake, Localization, and Retention for Enhanced Disease Diagnosis and Therapy. Aging and Disease, 16(1), 168–208. https://doi.org/10.14336/AD.2024.0206-1
Pérez-Ferreiro, M., M. Abelairas, A., Criado, A., Gómez, I. J., & Mosquera, J. (2023). Dendrimers: Exploring Their Wide Structural Variety and Applications. Polymers, 15(22), 4369. https://doi.org/10.3390/polym15224369
Shin, H. J., Kwak, M., Joo, S., & Lee, J. Y. (2022). Quantifying fluorescent nanoparticle uptake in mammalian cells using a plate reader. Scientific Reports, 12(1), 20146. https://doi.org/10.1038/s41598-022-24480-3
Shin, H., Kwak, M., Lee, T. G., & Lee, J. Y. (2020). Quantifying the level of nanoparticle uptake in mammalian cells using flow cytometry. Nanoscale, 12(29), 15743–15751. https://doi.org/10.1039/D0NR01627F
Singh, G., Myasnichenko, V. S., & Glomm, W. R. (2020). New insights into size-controlled reproducible synthesis of anisotropic Fe 3 O 4 nanoparticles: the importance of the reaction environment. Materials Advances, 1(5), 1077–1082. https://doi.org/10.1039/D0MA00275E
Soares, S., Pereira, C., Sousa, A. P., Oliveira, A. C., Sales, M. G., Correa-Duarte, M. A., Guerreiro, S. G., & Fernandes, R. (2023). Metabolic Disruption of Gold Nanospheres, Nanostars and Nanorods in Human Metastatic Prostate Cancer Cells. Cells, 12(5), 787. https://doi.org/10.3390/cells12050787
Soni, S. S., Kim, K. M., Sarkar, B., & Rodell, C. B. (2024). Uptake of Cyclodextrin Nanoparticles by Macrophages is Dependent on Particle Size and Receptor-Mediated Interactions. ACS Applied Bio Materials, 7(8), 4856–4866. https://doi.org/10.1021/acsabm.3c00985
Steckiewicz, K. P., Barcinska, E., Malankowska, A., Zauszkiewicz–Pawlak, A., Nowaczyk, G., Zaleska-Medynska, A., & Inkielewicz-Stepniak, I. (2019). Impact of gold nanoparticles shape on their cytotoxicity against human osteoblast and osteosarcoma in in vitro model. Evaluation of the safety of use and anti-cancer potential. Journal of Materials Science: Materials in Medicine, 30(2), 22. https://doi.org/10.1007/s10856-019-6221-2
Su, Y. Y., Jiang, X. Y., Zheng, L. J., Yang, Y. W., Yan, S. Y., Tian, Y., Tian, W., Liu, W. F., Teng, Z. G., Yao, H., Wang, S. J., & Zhang, L. J. (2023). Hybrid Au-star@Prussian blue for high-performance towards bimodal imaging and photothermal treatment. Journal of Colloid and Interface Science, 634, 601–609. https://doi.org/10.1016/j.jcis.2022.12.043
Sun, L., Liu, H., Ye, Y., Lei, Y., Islam, R., Tan, S., Tong, R., Miao, Y.-B., & Cai, L. (2023). Smart nanoparticles for cancer therapy. Signal Transduction and Targeted Therapy, 8(1), 418. https://doi.org/10.1038/s41392-023-01642-x
Thamizhchelvan, A. M., Ma, H., Wu, T., Nguyen, D., Padelford, J., Whitworth, T. J., Li, Y., Yang, L., & Mao, H. (2024). Shape-dependent cellular uptake of iron oxide nanorods: mechanisms of endocytosis and implications on cell labeling and cellular delivery. Nanoscale, 16(46), 21398–21415. https://doi.org/10.1039/D4NR02408G
Uhl, C. G., Gao, Y., Zhou, S., & Liu, Y. (2018). The shape effect on polymer nanoparticle transport in a blood vessel. RSC Advances, 8(15), 8089–8100. https://doi.org/10.1039/C8RA00033F
Vaidyanathan, S., Kaushik, M., Dougherty, C., Rattan, R., Goonewardena, S. N., Banaszak Holl, M. M., Monano, J., & DiMaggio, S. (2016). Increase in Dye:Dendrimer Ratio Decreases Cellular Uptake of Neutral Dendrimers in RAW Cells. ACS Biomaterials Science & Engineering, 2(9), 1540–1545. https://doi.org/10.1021/acsbiomaterials.6b00308
Vikas, Kumar, R., & Soni, S. (2023). Concentration-dependent photothermal conversion efficiency of gold nanoparticles under near-infrared laser and broadband irradiation. Beilstein Journal of Nanotechnology, 14, 205–217. https://doi.org/10.3762/bjnano.14.20
Wang, J., & Liu, G. (2018). Imaging Nano–Bio Interactions in the Kidney: Toward a Better Understanding of Nanoparticle Clearance. Angewandte Chemie International Edition, 57(12), 3008–3010. https://doi.org/10.1002/anie.201711705
Williams, R. M., Shah, J., Ng, B. D., Minton, D. R., Gudas, L. J., Park, C. Y., & Heller, D. A. (2015). Mesoscale Nanoparticles Selectively Target the Renal Proximal Tubule Epithelium. Nano Letters, 15(4), 2358–2364. https://doi.org/10.1021/nl504610d
Williams, R. M., Shah, J., Tian, H. S., Chen, X., Geissmann, F., Jaimes, E. A., & Heller, D. A. (2018). Selective Nanoparticle Targeting of the Renal Tubules. Hypertension, 71(1), 87–94. https://doi.org/10.1161/HYPERTENSIONAHA.117.09843
WOLINSKY, J., & GRINSTAFF, M. (2008). Therapeutic and diagnostic applications of dendrimers for cancer treatment☆. Advanced Drug Delivery Reviews, 60(9), 1037–1055. https://doi.org/10.1016/j.addr.2008.02.012
Wu, W., Luo, L., Wang, Y., Wu, Q., Dai, H.-B., Li, J.-S., Durkan, C., Wang, N., & Wang, G.-X. (2018). Endogenous pH-responsive nanoparticles with programmable size changes for targeted tumor therapy and imaging applications. Theranostics, 8(11), 3038–3058. https://doi.org/10.7150/thno.23459
Yue, C., Zhang, C., Alfranca, G., Yang, Y., Jiang, X., Yang, Y., Pan, F., Fuente, J. M. de la, & Cui, D. (2016). Near-Infrared Light Triggered ROS-activated Theranostic Platform based on Ce6-CPT-UCNPs for Simultaneous Fluorescence Imaging and Chemo-Photodynamic Combined Therapy. Theranostics, 6(4), 456–469. https://doi.org/10.7150/thno.14101
Zhakypov, A. S., Nemkayeva, R. R., Yerlanuly, Y., Tulegenova, M. A., Kurbanov, B. Y., Aitzhanov, M. B., Markhabayeva, A. A., & Gabdullin, M. T. (2023). Synthesis and in situ oxidation of copper micro- and nanoparticles by arc discharge plasma in liquid. Scientific Reports, 13(1), 15714. https://doi.org/10.1038/s41598-023-41631-2
Zhang, M., & Li, J. (2009). Carbon nanotube in different shapes. In Materials Today (Vol. 12, Issue 6, pp. 12–18). https://doi.org/10.1016/S1369-7021(09)70176-2
Agudo-Canalejo, J., & Lipowsky, R. (2016). Stabilization of membrane necks by adhesive particles, substrate surfaces, and constriction forces. Soft Matter, 12(39), 8155–8166. https://doi.org/10.1039/C6SM01481J
AlSawaftah, N. M., Awad, N. S., Pitt, W. G., & Husseini, G. A. (2022). pH-Responsive Nanocarriers in Cancer Therapy. Polymers, 14(5), 936. https://doi.org/10.3390/polym14050936
Avila, Y. I., Rebolledo, L. P., Leal Santos, N., Rawlins, B., Radwan, Y., Andrade-Muñoz, M., Skelly, E., Chandler, M. R., Andrade, L. N. S., Kim, T. J., Dobrovolskaia, M. A., & Afonin, K. A. (2025). Changes in Generations of PAMAM Dendrimers and Compositions of Nucleic Acid Nanoparticles Govern Delivery and Immune Recognition. ACS Biomaterials Science & Engineering, 11(6), 3726–3737. https://doi.org/10.1021/acsbiomaterials.5c00336
Banerjee, A., Qi, J., Gogoi, R., Wong, J., & Mitragotri, S. (2016). Role of nanoparticle size, shape and surface chemistry in oral drug delivery. Journal of Controlled Release, 238, 176–185. https://doi.org/10.1016/j.jconrel.2016.07.051
Barz, M., Parak, W. J., & Zentel, R. (2024). Concepts and Approaches to Reduce or Avoid Protein Corona Formation on Nanoparticles: Challenges and Opportunities. Advanced Science (Weinheim, Baden-Wurttemberg, Germany), 11(34), e2402935. https://doi.org/10.1002/advs.202402935
Behzadi, S., Serpooshan, V., Tao, W., Hamaly, M. A., Alkawareek, M. Y., Dreaden, E. C., Brown, D., Alkilany, A. M., Farokhzad, O. C., & Mahmoudi, M. (2017). Cellular uptake of nanoparticles: journey inside the cell. Chemical Society Reviews, 46(14), 4218–4244. https://doi.org/10.1039/c6cs00636a
Bertrand, N., Grenier, P., Mahmoudi, M., Lima, E. M., Appel, E. A., Dormont, F., Lim, J.-M., Karnik, R., Langer, R., & Farokhzad, O. C. (2017). Mechanistic understanding of in vivo protein corona formation on polymeric nanoparticles and impact on pharmacokinetics. Nature Communications, 8(1), 777. https://doi.org/10.1038/s41467-017-00600-w
Bhirde, A. A., Chikkaveeraiah, B. V., Srivatsan, A., Niu, G., Jin, A. J., Kapoor, A., Wang, Z., Patel, S., Patel, V., Gorbach, A. M., Leapman, R. D., Gutkind, J. S., Hight Walker, A. R., & Chen, X. (2014). Targeted Therapeutic Nanotubes Influence the Viscoelasticity of Cancer Cells to Overcome Drug Resistance. ACS Nano, 8(5), 4177–4189. https://doi.org/10.1021/nn501223q
Campu, A., Focsan, M., Lerouge, F., Borlan, R., Tie, L., Rugina, D., & Astilean, S. (2020). ICG-loaded gold nano-bipyramids with NIR activatable dual PTT-PDT therapeutic potential in melanoma cells. Colloids and Surfaces B: Biointerfaces, 194, 111213. https://doi.org/10.1016/j.colsurfb.2020.111213
Carnovale, C., Bryant, G., Shukla, R., & Bansal, V. (2019). Identifying Trends in Gold Nanoparticle Toxicity and Uptake: Size, Shape, Capping Ligand, and Biological Corona. ACS Omega, 4(1), 242–256. https://doi.org/10.1021/acsomega.8b03227
Cojocaru, E., Petriș, O. R., & Cojocaru, C. (2024). Nanoparticle-Based Drug Delivery Systems in Inhaled Therapy: Improving Respiratory Medicine. Pharmaceuticals, 17(8), 1059. https://doi.org/10.3390/ph17081059
Curthoys, N. P., & Moe, O. W. (2014). Proximal Tubule Function and Response to Acidosis. Clinical Journal of the American Society of Nephrology, 9(9), 1627–1638. https://doi.org/10.2215/CJN.10391012
Cybulski, P., Bravo, M., Chen, J. J.-K., Van Zundert, I., Krzyzowska, S., Taemaitree, F., Uji-i, H., Hofkens, J., Rocha, S., & Fortuni, B. (2025a). Nanoparticle accumulation and penetration in 3D tumor models: the effect of size, shape, and surface charge. Frontiers in Cell and Developmental Biology, 12. https://doi.org/10.3389/fcell.2024.1520078
Cybulski, P., Bravo, M., Chen, J. J.-K., Van Zundert, I., Krzyzowska, S., Taemaitree, F., Uji-i, H., Hofkens, J., Rocha, S., & Fortuni, B. (2025b). Nanoparticle accumulation and penetration in 3D tumor models: the effect of size, shape, and surface charge. Frontiers in Cell and Developmental Biology, 12. https://doi.org/10.3389/fcell.2024.1520078
Deivayanai, V. C., Thamarai, P., Karishma, S., Saravanan, A., Yaashikaa, P. R., Vickram, A. S., Hemavathy, R. V., Kumar, R. R., Rishikesavan, S., & Shruthi, S. (2025). Advances in nanoparticle-mediated cancer therapeutics: Current research and future perspectives. Cancer Pathogenesis and Therapy, 3(4), 293–308. https://doi.org/10.1016/j.cpt.2024.11.002
Dolai, J., Mandal, K., & Jana, N. R. (2021). Nanoparticle Size Effects in Biomedical Applications. ACS Applied Nano Materials, 4(7), 6471–6496. https://doi.org/10.1021/acsanm.1c00987
Eroglu, Z., Ozer, M. S., & Metin, O. (2023). Black Phosphorus Quantum Dots/Carbon Nitride-Reduced Graphene Oxide Ternary Heterojunction as a Multifunctional Metal-Free Photocatalyst for Photooxidation Reactions. ACS Sustainable Chemistry & Engineering, 11(19), 7560–7572. https://doi.org/10.1021/acssuschemeng.3c01055
Fan, Y., Zhang, W., Iqbal, Z., Li, X., Lin, Z., Wu, Z., Li, Q., Dong, H., Zhang, X., Gong, P., & Liu, P. (2024). Rod-shaped mesoporous silica nanoparticles reduce bufalin cardiotoxicity and inhibit colon cancer by blocking lipophagy. Lipids in Health and Disease, 23(1), 318. https://doi.org/10.1186/s12944-024-02301-y
Fang, W., Yu, K., Zhang, S., Jiang, L., Zheng, H., Huang, Q., & Li, F. (2024). Shape Matters: Impact of Mesoporous Silica Nanoparticle Morphology on Anti-Tumor Efficacy. Pharmaceutics, 16(5), 632. https://doi.org/10.3390/pharmaceutics16050632
Foroozandeh, P., & Aziz, A. A. (2018). Insight into Cellular Uptake and Intracellular Trafficking of Nanoparticles. Nanoscale Research Letters, 13(1), 339. https://doi.org/10.1186/s11671-018-2728-6
Gimondi, S., Vieira de Castro, J., Reis, R. L., Ferreira, H., & Neves, N. M. (2023). On the size-dependent internalization of sub-hundred polymeric nanoparticles. Colloids and Surfaces B: Biointerfaces, 225, 113245. https://doi.org/10.1016/j.colsurfb.2023.113245
Gospodinova, Z., Hristova-Panusheva, K., Kamenska, T., Antov, G., & Krasteva, N. (2025). Insights into cellular and molecular mechanisms of graphene oxide nanoparticles in photothermal therapy for hepatocellular carcinoma. Scientific Reports, 15(1), 15541. https://doi.org/10.1038/s41598-025-99317-w
Guo, Q., Pospischil, A., Bhuiyan, M., Jiang, H., Tian, H., Farmer, D., Deng, B., Li, C., Han, S.-J., Wang, H., Xia, Q., Ma, T.-P., Mueller, T., & Xia, F. (2016). Black Phosphorus Mid-Infrared Photodetectors with High Gain. Nano Letters, 16(7), 4648–4655. https://doi.org/10.1021/acs.nanolett.6b01977
Iqbal, S., Schneider, T.-J. K., Truong, T. T., Ulrich-Müller, R., Nguyen, P.-H., Ilyas, S., & Mathur, S. (2024). Carriers for hydrophobic drug molecules: lipid-coated hollow mesoporous silica particles, and the influence of shape and size on encapsulation efficiency. Nanoscale, 16(23), 11274–11289. https://doi.org/10.1039/D4NR01420K
Jiang, J., Hu, J., Li, M., Luo, M., Dong, B., Sitti, M., & Yan, X. (2025). NIR‐II Fluorescent Thermophoretic Nanomotors for Superficial Tumor Photothermal Therapy. Advanced Materials, 37(10). https://doi.org/10.1002/adma.202417440
Khajegi, P., & Rashidi-Huyeh, M. (2021). Optical Properties of Gold Nanoparticles: Shape and Size Effects. International Journal of Optics and Photonics, 15(1), 41–48. https://doi.org/10.52547/ijop.15.1.41
Kondorskiy, A. D., & Lebedev, V. S. (2021). Size and Shape Effects in Optical Spectra of Silver and Gold Nanoparticles. Journal of Russian Laser Research, 42(6), 697–712. https://doi.org/10.1007/s10946-021-10012-3
Korangath, P., Barnett, J. D., Sharma, A., Henderson, E. T., Stewart, J., Yu, S.-H., Kandala, S. K., Yang, C.-T., Caserto, J. S., Hedayati, M., Armstrong, T. D., Jaffee, E., Gruettner, C., Zhou, X. C., Fu, W., Hu, C., Sukumar, S., Simons, B. W., & Ivkov, R. (2020). Nanoparticle interactions with immune cells dominate tumor retention and induce T cell-mediated tumor suppression in models of breast cancer. Science Advances, 6(13), eaay1601. https://doi.org/10.1126/sciadv.aay1601
Kshirsagar, P. G., De Matteis, V., Pal, S., & Sangaru, S. S. (2023). Silver–Gold Alloy Nanoparticles (AgAu NPs): Photochemical Synthesis of Novel Biocompatible, Bimetallic Alloy Nanoparticles and Study of Their In Vitro Peroxidase Nanozyme Activity. Nanomaterials, 13(17), 2471. https://doi.org/10.3390/nano13172471
Lavín Flores, A., Medina-Berríos, N., Pantoja-Romero, W., Berríos Plaza, D., Kisslinger, K., Beltran-Huarac, J., Morell, G., & Weiner, B. R. (2024). Geometry and Surface Area Optimization in Iron Oxide Nanoparticles for Enhanced Magnetic Properties. ACS Omega. https://doi.org/10.1021/acsomega.4c03988
Li, Q., Liu, W., Liu, K., Dong, Z., Kong, W., Lu, X., Wei, Y., Wu, W., Yang, J., & Qi, J. (2024). The Role of Nanoparticle Morphology on Enhancing Delivery of Budesonide for Treatment of Inflammatory Bowel Disease. ACS Applied Materials & Interfaces, 16(26), 33081–33092. https://doi.org/10.1021/acsami.4c05214
Li, Y., Kröger, M., & Liu, W. K. (2015). Shape effect in cellular uptake of PEGylated nanoparticles: comparison between sphere, rod, cube and disk. Nanoscale, 7(40), 16631–16646. https://doi.org/10.1039/C5NR02970H
Liu, Y., Li, Y., Shen, W., Li, M., Wang, W., & Jin, X. (2024). Trend of albumin nanoparticles in oncology: a bibliometric analysis of research progress and prospects. Frontiers in Pharmacology, 15. https://doi.org/10.3389/fphar.2024.1409163
Lu, M., Liu, Y., Zhu, J., Shang, J., Bai, L., Jin, Z., Li, W., Hu, Y., Zheng, X., & Qian, J. (2025). Mapping the intellectual structure and emerging trends on nanomaterials in colorectal cancer: a bibliometric analysis from 2003 to 2024. Frontiers in Oncology, 14. https://doi.org/10.3389/fonc.2024.1514581
Lu, Y., Pan, X., Nie, Q., Zhou, Z., Dai, X., & Liu, O. (2023). Administration methods of lipid-based nanoparticle delivery systems for cancer treatment. Biomaterials Science, 11(11), 3800–3812. https://doi.org/10.1039/D3BM00219E
Lynn, A. Y., Shin, K., Eaton, D. A., Rose, M., Zhang, X., Ene, M., Grundler, J., Deschenes, E., Rivero, R., Bracaglia, L. G., Glazer, P. M., Stitelman, D. H., & Saltzman, W. M. (2025). Investigation of the protein corona and biodistribution profile of polymeric nanoparticles for intra-amniotic delivery. Biomaterials, 320, 123238. https://doi.org/10.1016/j.biomaterials.2025.123238
Ma, C., Zhang, J., Zhang, T., Sun, H., Wu, J., Shi, J., & Xie, Z. (2019). Comparing the Rod-Like and Spherical BODIPY Nanoparticles in Cellular Imaging. Frontiers in Chemistry, 7. https://doi.org/10.3389/fchem.2019.00765
Ma, X., Lee, S., Fei, X., Fang, G., Huynh, T., Chen, C., Chai, Z., Ge, C., & Zhou, R. (2020). Proteasome activity regulated by charged gold nanoclusters: Implications for neurodegenerative diseases. Nano Today, 35, 100933. https://doi.org/10.1016/j.nantod.2020.100933
Mai, B. T., Balakrishnan, P. B., Barthel, M. J., Piccardi, F., Niculaes, D., Marinaro, F., Fernandes, S., Curcio, A., Kakwere, H., Autret, G., Cingolani, R., Gazeau, F., & Pellegrino, T. (2019). Thermoresponsive Iron Oxide Nanocubes for an Effective Clinical Translation of Magnetic Hyperthermia and Heat-Mediated Chemotherapy. ACS Applied Materials & Interfaces, 11(6), 5727–5739. https://doi.org/10.1021/acsami.8b16226
Moscatiello, G. Y., Natale, C., Inserra, M., Morelli, A., Russo, L., Battajini, N., Sironi, L., Panzeri, D., Corbelli, A., De Luigi, A., Fiordaliso, F., Candiani, G., Bigini, P., & Diomede, L. (2025). The surface charge both influences the penetration and safety of polystyrene nanoparticles despite the protein corona formation. Environmental Science: Nano, 12(5), 2857–2870. https://doi.org/10.1039/D4EN00962B
Murugan, K., Choonara, Y. E., Kumar, P., Bijukumar, D., du Toit, L. C., & Pillay, V. (2015). Parameters and characteristics governing cellular internalization and trans-barrier trafficking of nanostructures. International Journal of Nanomedicine, 10, 2191–2206. https://doi.org/10.2147/IJN.S75615
Naumenko, V., Nikitin, A., Kapitanova, K., Melnikov, P., Vodopyanov, S., Garanina, A., Valikhov, M., Ilyasov, A., Vishnevskiy, D., Markov, A., Golyshev, S., Zhukov, D., Alieva, I., Abakumov, M., Chekhonin, V., & Majouga, A. (2019). Intravital microscopy reveals a novel mechanism of nanoparticles excretion in kidney. Journal of Controlled Release, 307, 368–378. https://doi.org/10.1016/j.jconrel.2019.06.026
Pang, C., Brunelli, A., Zhu, C., Hristozov, D., Liu, Y., Semenzin, E., Wang, W., Tao, W., Liang, J., Marcomini, A., Chen, C., & Zhao, B. (2015). Demonstrating approaches to chemically modify the surface of Ag nanoparticles in order to influence their cytotoxicity and biodistribution after single dose acute intravenous administration. Nanotoxicology, 1–11. https://doi.org/10.3109/17435390.2015.1024295
Peng, Y., Yang, Z., Sun, H., Li, J., Lan, X., & Liu, S. (2024). Nanomaterials in Medicine: Understanding Cellular Uptake, Localization, and Retention for Enhanced Disease Diagnosis and Therapy. Aging and Disease, 16(1), 168–208. https://doi.org/10.14336/AD.2024.0206-1
Pérez-Ferreiro, M., M. Abelairas, A., Criado, A., Gómez, I. J., & Mosquera, J. (2023). Dendrimers: Exploring Their Wide Structural Variety and Applications. Polymers, 15(22), 4369. https://doi.org/10.3390/polym15224369
Shin, H. J., Kwak, M., Joo, S., & Lee, J. Y. (2022). Quantifying fluorescent nanoparticle uptake in mammalian cells using a plate reader. Scientific Reports, 12(1), 20146. https://doi.org/10.1038/s41598-022-24480-3
Shin, H., Kwak, M., Lee, T. G., & Lee, J. Y. (2020). Quantifying the level of nanoparticle uptake in mammalian cells using flow cytometry. Nanoscale, 12(29), 15743–15751. https://doi.org/10.1039/D0NR01627F
Singh, G., Myasnichenko, V. S., & Glomm, W. R. (2020). New insights into size-controlled reproducible synthesis of anisotropic Fe 3 O 4 nanoparticles: the importance of the reaction environment. Materials Advances, 1(5), 1077–1082. https://doi.org/10.1039/D0MA00275E
Soares, S., Pereira, C., Sousa, A. P., Oliveira, A. C., Sales, M. G., Correa-Duarte, M. A., Guerreiro, S. G., & Fernandes, R. (2023). Metabolic Disruption of Gold Nanospheres, Nanostars and Nanorods in Human Metastatic Prostate Cancer Cells. Cells, 12(5), 787. https://doi.org/10.3390/cells12050787
Soni, S. S., Kim, K. M., Sarkar, B., & Rodell, C. B. (2024). Uptake of Cyclodextrin Nanoparticles by Macrophages is Dependent on Particle Size and Receptor-Mediated Interactions. ACS Applied Bio Materials, 7(8), 4856–4866. https://doi.org/10.1021/acsabm.3c00985
Steckiewicz, K. P., Barcinska, E., Malankowska, A., Zauszkiewicz–Pawlak, A., Nowaczyk, G., Zaleska-Medynska, A., & Inkielewicz-Stepniak, I. (2019). Impact of gold nanoparticles shape on their cytotoxicity against human osteoblast and osteosarcoma in in vitro model. Evaluation of the safety of use and anti-cancer potential. Journal of Materials Science: Materials in Medicine, 30(2), 22. https://doi.org/10.1007/s10856-019-6221-2
Su, Y. Y., Jiang, X. Y., Zheng, L. J., Yang, Y. W., Yan, S. Y., Tian, Y., Tian, W., Liu, W. F., Teng, Z. G., Yao, H., Wang, S. J., & Zhang, L. J. (2023). Hybrid Au-star@Prussian blue for high-performance towards bimodal imaging and photothermal treatment. Journal of Colloid and Interface Science, 634, 601–609. https://doi.org/10.1016/j.jcis.2022.12.043
Sun, L., Liu, H., Ye, Y., Lei, Y., Islam, R., Tan, S., Tong, R., Miao, Y.-B., & Cai, L. (2023). Smart nanoparticles for cancer therapy. Signal Transduction and Targeted Therapy, 8(1), 418. https://doi.org/10.1038/s41392-023-01642-x
Thamizhchelvan, A. M., Ma, H., Wu, T., Nguyen, D., Padelford, J., Whitworth, T. J., Li, Y., Yang, L., & Mao, H. (2024). Shape-dependent cellular uptake of iron oxide nanorods: mechanisms of endocytosis and implications on cell labeling and cellular delivery. Nanoscale, 16(46), 21398–21415. https://doi.org/10.1039/D4NR02408G
Uhl, C. G., Gao, Y., Zhou, S., & Liu, Y. (2018). The shape effect on polymer nanoparticle transport in a blood vessel. RSC Advances, 8(15), 8089–8100. https://doi.org/10.1039/C8RA00033F
Vaidyanathan, S., Kaushik, M., Dougherty, C., Rattan, R., Goonewardena, S. N., Banaszak Holl, M. M., Monano, J., & DiMaggio, S. (2016). Increase in Dye:Dendrimer Ratio Decreases Cellular Uptake of Neutral Dendrimers in RAW Cells. ACS Biomaterials Science & Engineering, 2(9), 1540–1545. https://doi.org/10.1021/acsbiomaterials.6b00308
Vikas, Kumar, R., & Soni, S. (2023). Concentration-dependent photothermal conversion efficiency of gold nanoparticles under near-infrared laser and broadband irradiation. Beilstein Journal of Nanotechnology, 14, 205–217. https://doi.org/10.3762/bjnano.14.20
Wang, J., & Liu, G. (2018). Imaging Nano–Bio Interactions in the Kidney: Toward a Better Understanding of Nanoparticle Clearance. Angewandte Chemie International Edition, 57(12), 3008–3010. https://doi.org/10.1002/anie.201711705
Williams, R. M., Shah, J., Ng, B. D., Minton, D. R., Gudas, L. J., Park, C. Y., & Heller, D. A. (2015). Mesoscale Nanoparticles Selectively Target the Renal Proximal Tubule Epithelium. Nano Letters, 15(4), 2358–2364. https://doi.org/10.1021/nl504610d
Williams, R. M., Shah, J., Tian, H. S., Chen, X., Geissmann, F., Jaimes, E. A., & Heller, D. A. (2018). Selective Nanoparticle Targeting of the Renal Tubules. Hypertension, 71(1), 87–94. https://doi.org/10.1161/HYPERTENSIONAHA.117.09843
WOLINSKY, J., & GRINSTAFF, M. (2008). Therapeutic and diagnostic applications of dendrimers for cancer treatment☆. Advanced Drug Delivery Reviews, 60(9), 1037–1055. https://doi.org/10.1016/j.addr.2008.02.012
Wu, W., Luo, L., Wang, Y., Wu, Q., Dai, H.-B., Li, J.-S., Durkan, C., Wang, N., & Wang, G.-X. (2018). Endogenous pH-responsive nanoparticles with programmable size changes for targeted tumor therapy and imaging applications. Theranostics, 8(11), 3038–3058. https://doi.org/10.7150/thno.23459
Yue, C., Zhang, C., Alfranca, G., Yang, Y., Jiang, X., Yang, Y., Pan, F., Fuente, J. M. de la, & Cui, D. (2016). Near-Infrared Light Triggered ROS-activated Theranostic Platform based on Ce6-CPT-UCNPs for Simultaneous Fluorescence Imaging and Chemo-Photodynamic Combined Therapy. Theranostics, 6(4), 456–469. https://doi.org/10.7150/thno.14101
Zhakypov, A. S., Nemkayeva, R. R., Yerlanuly, Y., Tulegenova, M. A., Kurbanov, B. Y., Aitzhanov, M. B., Markhabayeva, A. A., & Gabdullin, M. T. (2023). Synthesis and in situ oxidation of copper micro- and nanoparticles by arc discharge plasma in liquid. Scientific Reports, 13(1), 15714. https://doi.org/10.1038/s41598-023-41631-2
Zhang, M., & Li, J. (2009). Carbon nanotube in different shapes. In Materials Today (Vol. 12, Issue 6, pp. 12–18). https://doi.org/10.1016/S1369-7021(09)70176-2
